Reciprocal influences of CB1 cannabinoid receptor agonists on ERK and JNK signalling in N1E-115 cells.
Agonists acting at the CB1 cannabinoid receptor in N1E-115 neuroblastoma cells were found to activate MAPK family members with reciprocal efficacies. Thus, HU 210 robustly increased phosphorylation of ERK1/2 whereas CP 55,940 was more effective in activating JNK. The use of selected kinase inhibitors confirmed that distinct signalling cascades were involved in these responses. This reciprocal control of MAPK activity was correlated with the observation that HU 210- and CP 55,940-mediated regulations of tyrosine hydroxylase gene expression were respectively impaired by MEK and JNK inhibitors. These data indicate that complex interactions of the CB1 receptor with intracellular signalling partners controlling MAPK activities may explain the apparent disparities in cellular responses to functional selective agonists.
Bosier
Barbara
B
Unité de Chimie Pharmaceutique et de Radiopharmacie (UCL 7340), Université catholique de Louvain, 73 40, Av E.Mounier, B-1200 Brussels, Belgium.
Lambert
Didier M
DM
Hermans
Emmanuel
E
D000818:Animals; D045744:Cell Line, Tumor; D003511:Cyclohexanols / Q000494:pharmacology*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D003511:Cyclohexanols; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C062018:HU 211